FSP1 / AIFM2

evidence_span

{"source_cache": "artifacts/k2-research/36788244.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5fda09197d386351a1b1d261c9b385db36e02eab0c238bf18599d7086b501f93", "start_char": 0, "end_char": 1359, "text_sha256": "5fda09197d386351a1b1d261c9b385db36e02eab0c238bf18599d7086b501f93"}

experimental_model

Genome-wide CRISPR screen and reporter biochemistry

exposure

FSP1 knockout/inhibition and DHODH comparison

limitations

Supports cycle biochemistry; a different ferroptosis defense enzyme need not share the same vitamin K function.

nutrient_topic

Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family

organism

Human vitamin K-dependent reporter cells

plain_language

The antioxidant enzyme also helps supply cofactor for protein modification.

primary_references

[k2-p36788244] A genome-wide CRISPR-Cas9 knockout screen identifies FSP1 as the warfarin-resistant vitamin K reductase. (2023). https://pubmed.ncbi.nlm.nih.gov/36788244/ DOI: 10.1038/s41467-023-36446-8

tissue_or_cell_type

Warfarin-resistant quinone reduction

Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 825–836

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genome-wide CRISPR screen and reporter biochemistry · source_derived_draft · unverified_draft

### k2-fsp1-carboxylation A CRISPR screen independently identified FSP1 as the warfarin-resistant vitamin K reductase; FSP1 inhibition impaired vitamin K-dependent carboxylation. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The antioxidant enzyme also helps supply cofactor for protein modification. organism: Human vitamin K-dependent reporter cells tissue_or_cell_type: Warfarin-resistant quinone reduction experimental_model: Genome-wide CRISPR screen and reporter biochemistry limitations: Supports cycle biochemistry; a different ferroptosis defense enzyme need not share the same vitamin K function. exposure: FSP1 knockout/inhibition and DHODH comparison evidence_span: {"source_cache": "artifacts/k2-research/36788244.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5fda09197d386351a1b1d261c9b385db36e02eab0c238bf18599d7086b501f93", "start_char": 0, "end_char": 1359, "text_sha256": "5fda09197d386351a1b1d261c9b385db36e02eab0c238bf18599d7086b501f93"} [k2-p36788244] A genome-wide CRISPR-Cas9 knockout screen identifies FSP1 as the warfarin-resistant vitamin K reductase. (2023). https://pubmed.ncbi.nlm.nih.gov/36788244/ DOI: 10.1038/s41467-023-36446-8

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/k2-research/35922516.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a75e4881732cbe87173197db393b42d49fc6e8110df919fed8d63b16c9877da6", "start_char": 16083, "end_char": 16259, "text_sha256": "942e81f7fca3a59aecc9d6cfcdc008e88931de54074e63eeb96c71af3d236eec"}

experimental_model

Enzyme/liposome chemistry, knockout cells and warfarin-exposed mice

exposure

MK-4/K1, NAD(P)H, FSP1 loss and inhibitors

limitations

Preclinical experiments; not a demonstrated oral MK-7 treatment for ferroptosis-related disease or a self-treatment regimen for anticoagulant poisoning.

nutrient_topic

Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family

organism

Human recombinant FSP1, mammalian cells and mice

plain_language

The FSP1 pathway and selenium-dependent GPX4 defense are connected but not the same mechanism.

primary_references

[k2-p35922516] A non-canonical vitamin K cycle is a potent ferroptosis suppressor. (2022). https://pubmed.ncbi.nlm.nih.gov/35922516/ DOI: 10.1038/s41586-022-05022-3

tissue_or_cell_type

Lipid peroxidation and vitamin K reduction

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 812–823

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Enzyme/liposome chemistry, knockout cells and warfarin-exposed mice · source_derived_draft · unverified_draft

### k2-fsp1-gpx4-parallel Cells lacking both GPX4 and FSP1 required higher K1/MK-4 concentrations to prevent ferroptosis than cells lacking GPX4 alone. Condition category: machinery_impairment nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The FSP1 pathway and selenium-dependent GPX4 defense are connected but not the same mechanism. organism: Human recombinant FSP1, mammalian cells and mice tissue_or_cell_type: Lipid peroxidation and vitamin K reduction experimental_model: Enzyme/liposome chemistry, knockout cells and warfarin-exposed mice limitations: Preclinical experiments; not a demonstrated oral MK-7 treatment for ferroptosis-related disease or a self-treatment regimen for anticoagulant poisoning. exposure: MK-4/K1, NAD(P)H, FSP1 loss and inhibitors evidence_span: {"source_cache": "artifacts/k2-research/35922516.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a75e4881732cbe87173197db393b42d49fc6e8110df919fed8d63b16c9877da6", "start_char": 16083, "end_char": 16259, "text_sha256": "942e81f7fca3a59aecc9d6cfcdc008e88931de54074e63eeb96c71af3d236eec"} [k2-p35922516] A non-canonical vitamin K cycle is a potent ferroptosis suppressor. (2022). https://pubmed.ncbi.nlm.nih.gov/35922516/ DOI: 10.1038/s41586-022-05022-3

evidence_span

{"source_cache": "artifacts/k2-research/35922516.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3bd5750fd2d12a754ad4237018851391c6b5b80bac6ad58307321fb7c3042c5a", "start_char": 0, "end_char": 1403, "text_sha256": "3bd5750fd2d12a754ad4237018851391c6b5b80bac6ad58307321fb7c3042c5a"}

experimental_model

Enzyme/liposome chemistry, knockout cells and warfarin-exposed mice

exposure

MK-4/K1, NAD(P)H, FSP1 loss and inhibitors

limitations

Preclinical experiments; not a demonstrated oral MK-7 treatment for ferroptosis-related disease or a self-treatment regimen for anticoagulant poisoning.

nutrient_topic

Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family

organism

Human recombinant FSP1, mammalian cells and mice

plain_language

A niacin-derived electron donor helps regenerate the reduced antioxidant form.

primary_references

[k2-p35922516] A non-canonical vitamin K cycle is a potent ferroptosis suppressor. (2022). https://pubmed.ncbi.nlm.nih.gov/35922516/ DOI: 10.1038/s41586-022-05022-3

tissue_or_cell_type

Lipid peroxidation and vitamin K reduction

Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 773–784

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Enzyme/liposome chemistry, knockout cells and warfarin-exposed mice · source_derived_draft · unverified_draft

### k2-fsp1-k-reduction FSP1 reduced vitamin K quinones to radical-trapping hydroquinones using NAD(P)H. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A niacin-derived electron donor helps regenerate the reduced antioxidant form. organism: Human recombinant FSP1, mammalian cells and mice tissue_or_cell_type: Lipid peroxidation and vitamin K reduction experimental_model: Enzyme/liposome chemistry, knockout cells and warfarin-exposed mice limitations: Preclinical experiments; not a demonstrated oral MK-7 treatment for ferroptosis-related disease or a self-treatment regimen for anticoagulant poisoning. exposure: MK-4/K1, NAD(P)H, FSP1 loss and inhibitors evidence_span: {"source_cache": "artifacts/k2-research/35922516.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3bd5750fd2d12a754ad4237018851391c6b5b80bac6ad58307321fb7c3042c5a", "start_char": 0, "end_char": 1403, "text_sha256": "3bd5750fd2d12a754ad4237018851391c6b5b80bac6ad58307321fb7c3042c5a"} [k2-p35922516] A non-canonical vitamin K cycle is a potent ferroptosis suppressor. (2022). https://pubmed.ncbi.nlm.nih.gov/35922516/ DOI: 10.1038/s41586-022-05022-3

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/k2-research/35922516.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a75e4881732cbe87173197db393b42d49fc6e8110df919fed8d63b16c9877da6", "start_char": 15449, "end_char": 16082, "text_sha256": "689a74e99dd668d48baef5232109dbf2898ba3adca2999a83a7bb24b321420c0"}

experimental_model

Enzyme/liposome chemistry, knockout cells and warfarin-exposed mice

exposure

MK-4/K1, NAD(P)H, FSP1 loss and inhibitors

limitations

Preclinical experiments; not a demonstrated oral MK-7 treatment for ferroptosis-related disease or a self-treatment regimen for anticoagulant poisoning.

nutrient_topic

Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family

organism

Human recombinant FSP1, mammalian cells and mice

plain_language

Providing the quinone did not fully substitute for an appropriately located working reductase.

primary_references

[k2-p35922516] A non-canonical vitamin K cycle is a potent ferroptosis suppressor. (2022). https://pubmed.ncbi.nlm.nih.gov/35922516/ DOI: 10.1038/s41586-022-05022-3

tissue_or_cell_type

Lipid peroxidation and vitamin K reduction

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 799–810

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Enzyme/liposome chemistry, knockout cells and warfarin-exposed mice · source_derived_draft · unverified_draft

### k2-fsp1-loss FSP1 knockout diminished MK-4 and K1 protection; wild-type FSP1 rescued protection while its myristoylation-defective G2A mutant did not. Condition category: machinery_impairment nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Providing the quinone did not fully substitute for an appropriately located working reductase. organism: Human recombinant FSP1, mammalian cells and mice tissue_or_cell_type: Lipid peroxidation and vitamin K reduction experimental_model: Enzyme/liposome chemistry, knockout cells and warfarin-exposed mice limitations: Preclinical experiments; not a demonstrated oral MK-7 treatment for ferroptosis-related disease or a self-treatment regimen for anticoagulant poisoning. exposure: MK-4/K1, NAD(P)H, FSP1 loss and inhibitors evidence_span: {"source_cache": "artifacts/k2-research/35922516.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a75e4881732cbe87173197db393b42d49fc6e8110df919fed8d63b16c9877da6", "start_char": 15449, "end_char": 16082, "text_sha256": "689a74e99dd668d48baef5232109dbf2898ba3adca2999a83a7bb24b321420c0"} [k2-p35922516] A non-canonical vitamin K cycle is a potent ferroptosis suppressor. (2022). https://pubmed.ncbi.nlm.nih.gov/35922516/ DOI: 10.1038/s41586-022-05022-3

evidence_span

{"source_cache": "artifacts/coq10-research/37407687.publisher-preview.txt", "locator": "Primary public publisher preview, reference superscripts removed; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dd04682c5ac5215eff4a195cf2fcff7c5f6cf59eb659cc5710e6a2ecd09b0529", "start_char": 0, "end_char": 477, "text_sha256": "dd04682c5ac5215eff4a195cf2fcff7c5f6cf59eb659cc5710e6a2ecd09b0529"}

experimental_model

Primary experimental Matters Arising; public publisher preview

exposure

DHODH inhibitors at different concentrations

limitations

Public preview only; exact dose-response tables not extracted. Do not deny all DHODH effects or invent a universal concentration cutoff.

nutrient_topic

Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system

organism

Cancer-cell inhibitor and genetic comparisons

plain_language

A drug can affect a second enzyme, changing the explanation of its result.

primary_references

[coq10-p37407687] DHODH inhibitors sensitize to ferroptosis by FSP1 inhibition. (2023). https://pubmed.ncbi.nlm.nih.gov/37407687/ DOI: 10.1038/s41586-023-06269-0

tissue_or_cell_type

DHODH versus FSP1 attribution

Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 840–851

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary experimental Matters Arising; public publisher preview · source_derived_draft · unverified_draft

### coq10-dhodh-offtarget The 2023 study attributed strong ferroptosis sensitization by high concentrations of DHODH inhibitors to concurrent FSP1 inhibition. Condition category: normal nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A drug can affect a second enzyme, changing the explanation of its result. organism: Cancer-cell inhibitor and genetic comparisons tissue_or_cell_type: DHODH versus FSP1 attribution experimental_model: Primary experimental Matters Arising; public publisher preview limitations: Public preview only; exact dose-response tables not extracted. Do not deny all DHODH effects or invent a universal concentration cutoff. exposure: DHODH inhibitors at different concentrations evidence_span: {"source_cache": "artifacts/coq10-research/37407687.publisher-preview.txt", "locator": "Primary public publisher preview, reference superscripts removed; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dd04682c5ac5215eff4a195cf2fcff7c5f6cf59eb659cc5710e6a2ecd09b0529", "start_char": 0, "end_char": 477, "text_sha256": "dd04682c5ac5215eff4a195cf2fcff7c5f6cf59eb659cc5710e6a2ecd09b0529"} [coq10-p37407687] DHODH inhibitors sensitize to ferroptosis by FSP1 inhibition. (2023). https://pubmed.ncbi.nlm.nih.gov/37407687/ DOI: 10.1038/s41586-023-06269-0

evidence_span

{"source_cache": "artifacts/coq10-research/31634899.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1e96f6d5aed6def29533d907cd9ae90bc287d3f7beb6b9447aec3308d57a0dfe", "start_char": 0, "end_char": 1818, "text_sha256": "1e96f6d5aed6def29533d907cd9ae90bc287d3f7beb6b9447aec3308d57a0dfe"}

experimental_model

Expression cloning and cell-death experiments

exposure

GPX4 deletion or inhibitors and FSP1 manipulation

limitations

Cancer-cell defense mechanism; preventing ferroptosis is not always a desirable disease outcome and oral CoQ benefit is not tested.

nutrient_topic

Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system

organism

Human cancer-cell models

plain_language

The antioxidant form must be regenerated using reducing power.

primary_references

[coq10-p31634899] FSP1 is a glutathione-independent ferroptosis suppressor. (2019). https://pubmed.ncbi.nlm.nih.gov/31634899/ DOI: 10.1038/s41586-019-1707-0

tissue_or_cell_type

FSP1-CoQ antioxidant pathway

Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 801–812

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Expression cloning and cell-death experiments · source_derived_draft · unverified_draft

### coq10-fsp1-nadph FSP1 used NAD(P)H to regenerate the reduced CoQ pool that traps lipid peroxyl radicals. Condition category: normal nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The antioxidant form must be regenerated using reducing power. organism: Human cancer-cell models tissue_or_cell_type: FSP1-CoQ antioxidant pathway experimental_model: Expression cloning and cell-death experiments limitations: Cancer-cell defense mechanism; preventing ferroptosis is not always a desirable disease outcome and oral CoQ benefit is not tested. exposure: GPX4 deletion or inhibitors and FSP1 manipulation evidence_span: {"source_cache": "artifacts/coq10-research/31634899.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1e96f6d5aed6def29533d907cd9ae90bc287d3f7beb6b9447aec3308d57a0dfe", "start_char": 0, "end_char": 1818, "text_sha256": "1e96f6d5aed6def29533d907cd9ae90bc287d3f7beb6b9447aec3308d57a0dfe"} [coq10-p31634899] FSP1 is a glutathione-independent ferroptosis suppressor. (2019). https://pubmed.ncbi.nlm.nih.gov/31634899/ DOI: 10.1038/s41586-019-1707-0

cross_nutrient

Shared GPX4 connects retinoid signaling to the selenium collection; no proven supplementation synergy.

experimental_model

HT-1080 cells; pharmacological ATRA.

limitations

Direct promoter binding and dietary selenium replacement were not tested.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Homo sapiens

plain_language

Retinoid signaling reached existing ferroptosis-defense machinery.

primary_references

[va-berndt2024] Suppression of ferroptosis by vitamin A or radical-trapping antioxidants is essential for neuronal development (2024). https://pubmed.ncbi.nlm.nih.gov/39218970/ DOI: 10.1038/s41467-024-51996-1

tissue_or_cell_type

Human cell line

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1811–1821

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · HT-1080 cells; pharmacological ATRA. · source_derived_draft · unverified_draft

### va-atra-ferroptosis-regulators ATRA increased GPX4/FSP1 protein and GCH1 transcripts; RAR blockade suppressed the transcript responses. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Retinoid signaling reached existing ferroptosis-defense machinery. organism: Homo sapiens tissue_or_cell_type: Human cell line experimental_model: HT-1080 cells; pharmacological ATRA. limitations: Direct promoter binding and dietary selenium replacement were not tested. cross_nutrient: Shared GPX4 connects retinoid signaling to the selenium collection; no proven supplementation synergy. [va-berndt2024] Suppression of ferroptosis by vitamin A or radical-trapping antioxidants is essential for neuronal development (2024). https://pubmed.ncbi.nlm.nih.gov/39218970/ DOI: 10.1038/s41467-024-51996-1